JAMA | Review
Medications for Obesity A Review
JAMA | 評論肥胖藥物的回顧

Kimberly A. Gudzune, MD, MPH; Robert F. Kushner, MD, MS
金伯莉·A·古茲恩，醫學博士，公共衛生碩士；羅伯特·F·庫什納，醫學博士，碩士

Abstract 摘要

IMPORTANCE Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia
重要性肥胖影響全球約 19%的女性和 14%的男性，並與增加的發病率相關。抗肥胖藥物（AOMs）改變影響食慾的生物過程，並顯著改善結果，如 2 型糖尿病、高血壓和血脂異常。

OBSERVATIONS AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than $25 %$ of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately $20 %$ of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16964 participants), phentermine-topiramate was associated with $8.0 %$ greater weight loss ( 5 RCTs; 3407 participants), naltrexone-bupropion was associated with $4.1 %$ greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with $11.4 %$ greater weight loss ( 5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with $12.4 %$ greater weight loss (6 RCTs; 1972 participants).
觀察結果 AOMs 應與生活方式干預結合使用，並可根據其作用機制進行分類。奧利司他改變消化道的吸收，並在超過 $25 %$ 的患者中引起腸胃不良反應，如油性糞便斑點和急迫感。中樞作用藥物，如芬特明-托吡酯和納曲酮-布普洛尼，調節大腦中的食慾，並在約 $20 %$ 的患者中與便秘相關，儘管其他不良反應（例如，感覺異常、噁心）的發生率因藥物而異。基於營養刺激的荷爾蒙藥物，如利拉魯肽、塞馬魯肽和替格魯肽，模仿改變中樞食慾調節的腸胰荷爾蒙的作用，並提供多種心代謝減重益處。這些藥物的不良反應包括噁心（28%-44%）、腹瀉（21%-30%）和便秘（11%-24%）。成人肥胖藥物的相對效力已在綜合分析中進行研究。與安慰劑相比，奧利司他與 3.1%的體重減輕相關（52 項隨機臨床試驗[RCTs]；16964 名參與者），芬特明-托吡酯與 $8.0 %$ 的體重減輕相關（5 項 RCTs；3407 名參與者），納曲酮-布普洛尼與 $4.1 %$ 的體重減輕相關（6 項 RCTs；9949 名參與者），利拉魯肽與 4.7%的體重減輕相關（18 項 RCTs；6321 名參與者），塞馬魯肽與 $11.4 %$ 的體重減輕相關（5 項 RCTs；4421 名參與者），而提澤帕肽 15 毫克與 $12.4 %$ 的體重減輕相關（6 項 RCTs；1972 名參與者）。

CONCLUSION AND RELEVANCE Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.
結論與相關性肥胖與增加的發病率有關。抗肥胖藥物是改善減重和健康結果的有效輔助療法，與生活方式改變相結合。

JAMA. doi:10.1001/jama.2024.10816
Published online July 22, 2024.
於 2024 年 7 月 22 日在線發佈。

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Author Affiliations: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (Gudzune); Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Gudzune); Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Kushner); Department of Medical Education, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Kushner).
作者隸屬機構：馬里蘭州巴爾的摩約翰霍普金斯大學醫學院內科部（Gudzune）；馬里蘭州巴爾的摩約翰霍普金斯布隆伯格公共衛生學院健康政策與管理系（Gudzune）；伊利諾伊州芝加哥西北大學范伯格醫學院內科部（Kushner）；伊利諾伊州芝加哥西北大學范伯格醫學院醫學教育部（Kushner）。
Corresponding Author: Robert F. Kushner, MD, MS, 645 N Michigan Ave, Ste 530, Chicago, IL 60611 (rkushner@northwestern.edu).
通訊作者：羅伯特·F·庫什納，醫學博士，碩士，645 N 密歇根大道，530 室，芝加哥，IL 60611（rkushner@northwestern.edu）。
Section Editor: Kristin Walter, MD, Deputy Editor.
編輯部主任：克里斯汀·沃爾特醫生，副編輯。

Obesity is a global public health problem associated with an increased prevalence of multiple chronic conditions compared with individuals without obesity.

^{1}

Since 1999, the prevalence of obesity among adults, defined as a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 30 or greater, has risen from

30 %

42 %

in the US and is projected to affect nearly 1 in 2 adults by

2030 .^{2}

Worldwide, obesity now affects

19 %

of women and

14 %

of men.

^{3}

Lifestyle management is important for obesity treatment, but is often associated with weight regain due to counterregulatory physiologic changes that impair metabolism and increase appetite.

^{4}

Antiobesity medications (AOMs) affect appetite dysregulation associated with obesity, thereby achieving and sustaining greater weight loss.

^{5}

Multiple obesity treatment guidelines recommend pharmacotherapy in conjunction with lifestyle modification.

^{6 - 10}

The US Food and Drug Administration (FDA) has approved multiple AOMs,
肥胖是一個全球公共健康問題，與多種慢性疾病的發病率增加有關，與沒有肥胖的個體相比。自 1999 年以來，在美國，定義為體重指數（BMI，計算方式為體重（公斤）除以身高（米）的平方）為 30 或更高的成年人肥胖率已從

30 %

上升至

42 %

，並預計到

2030 .^{2}

將影響近一半的成年人。全球範圍內，肥胖現在影響

19 %

的女性和

14 %

的男性。生活方式管理對於肥胖治療至關重要，但通常與體重反彈有關，這是由於反調節生理變化影響新陳代謝並增加食慾。抗肥胖藥物（AOMs）影響與肥胖相關的食慾失調，從而實現並維持更大的體重減輕。多項肥胖治療指導方針建議將藥物治療與生活方式改變結合使用。美國食品和藥物管理局（FDA）已批准多種 AOMs，
which are indicated for adults with a BMI of 30 or greater or for adults with a BMI of 27 or greater with weight-related comorbidities, such as type 2 diabetes, hypertension, or dyslipidemia.

^{6 - 9}

AOMs are also indicated for adolescents (aged

\geq 12

years) with BMI at or above the 95th percentile for age and sex.

^{10}

Insufficient evidence exists for AOM use in children younger than 12 years.

^{10}

Because adults of Asian and Southeast Asian ancestry experience obesity-related complications at lower BMIs, lower thresholds may be considered for AOM initiation in this population (BMI

\geq 27

or BMI

\geq 25

with weight-related comorbidities).

^{11}

This review summarizes the efficacy and safety of AOMs. Currently available AOMs are presented in 3 groups based on their mechanisms of action: intragastrointestinal medications (orlistat), centrally acting medications (phentermine, phentermine-topiramate, naltrexone-bupropion), and nutrient-stimulated hormone-based medications (liraglutide, semaglutide, tirzepatide) (Figure 1).
適用於 BMI 為 30 或以上的成年人，或 BMI 為 27 或以上且有與體重相關的合併症（如 2 型糖尿病、高血壓或血脂異常）的成年人。

^{6 - 9}

AOM 也適用於 BMI 達到或超過年齡和性別的第 95 百分位數的青少年（年齡

\geq 12

歲）。

^{10}

對於 12 歲以下的兒童，AOM 的使用證據不足。

^{10}

由於亞洲和東南亞血統的成年人在較低的 BMI 下會出現與肥胖相關的併發症，因此在這一人群中，AOM 啟動的 BMI 閾值可以考慮降低（BMI

\geq 27

或 BMI

\geq 25

且有與體重相關的合併症）。

^{11}

本評估總結了 AOM 的療效和安全性。目前可用的 AOM 根據其作用機制分為三組：腸內藥物（奧利司他）、中樞作用藥物（芬特明、芬特明-托吡酯、納曲酮-布普品）和營養刺激激素基藥物（利拉魯肽、塞馬魯肽、提澤帕肽）（圖 1）。

Figure 1. Mechanisms of Action and Common Adverse Effects of 3 Classes of Antiobesity Medication
圖 1. 三類抗肥胖藥物的作用機制及常見不良反應

AMPA indicates a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GABA,

γ

-aminobutyric acid; GIP, glucose-dependent insulinotropic polypeptide GLP-1, glucagon-like peptide 1.
AMPA 表示 α-氨基-3-羥基-5-甲基-4-異噁唑丙酸；GABA，

γ

-氨基丁酸；GIP，葡萄糖依賴性胰島素促進多肽 GLP-1，胰高血糖素樣肽 1。

Methods 方法

A literature search of PubMed was conducted between January 1, 2015, and February 27, 2024, using the following search terms: antiobesity agents, obesity drug therapy, and obesity pharmacotherapy. The search was limited to randomized clinical trials (RCTs), systematic reviews, and practice guidelines. A total of 744 articles were identified and 88 were included, consisting of 6 clinical practice guidelines, 5 systematic reviews, 4 meta-analyses, 43 RCTs, 9
在 2015 年 1 月 1 日至 2024 年 2 月 27 日之間，對 PubMed 進行了文獻搜索，使用的搜索詞包括：抗肥胖劑、肥胖藥物治療和肥胖藥物療法。搜索限制於隨機對照試驗（RCTs）、系統評價和實踐指導。共識別出 744 篇文章，並納入 88 篇，其中包括 6 項臨床實踐指導、5 項系統評價、4 項荟萃分析、43 項 RCT 和 9 項。
observational studies, 17 reviews, 2 study designs/baseline trial data, 2 secondary analyses of trial data, 1 consensus statement, and 3 perspectives (the systematic reviews and meta-analyses were not mutually exclusive).
觀察性研究、17 篇評論、2 種研究設計/基線試驗數據、2 項試驗數據的次級分析、1 份共識聲明，以及 3 個觀點（系統評價和統合分析並不互相排斥）。

Intragastrointestinal Medications
腸胃內用藥物

Currently, only 1FDA-approved AOM, orlistat, works by blocking fat absorption in the gastrointestinal (GI) tract. In the lumen of the stomach and small intestine, orlistat forms a covalent bond with the active site of intestinal lipases, blocking digestion and absorption of
目前，唯一獲得 FDA 批准的 AOM，奧利司他，通過阻止脂肪在胃腸道（GI）中的吸收來發揮作用。在胃和小腸的腔內，奧利司他與腸道脂肪酶的活性位點形成共價鍵，阻止消化和吸收。

Figure 2. Percentage of Adults With Obesity Without Diabetes Achieving Specific Weight-Loss Targets by Antiobesity Medication
圖 2. 無糖尿病的成人肥胖者達成特定減重目標的百分比，按抗肥胖藥物劃分

Observed percentages of adult participants with overweight/obesity and without diabetes from randomized clinical trials who achieved categorical body weight reductions of at least

5 %, 10 %, 15 %, 20 %

, and

25 %

from baseline while taking the study drug. Results from 1 trial for the following antiobesity medications are presented: orlistat 120 mg 3 times daily ( 52 weeks),

^{16}

phentermine-topiramate

15 / 92 mg

daily ( 56 weeks),

^{17}

naltrexone-bupropion
觀察到的成年參與者中，超重/肥胖且無糖尿病的百分比來自隨機臨床試驗，這些參與者在服用研究藥物期間達到了至少

5 %, 10 %, 15 %, 20 %

和

25 %

的體重減少。以下抗肥胖藥物的 1 項試驗結果如下：奧利司他 120 毫克每日 3 次（52 週），

^{16}

苯丁胺-托吡酯

15 / 92 mg

每日（56 週），

^{17}

納曲酮-布普洛尼。

32/360 mg total daily dose ( 56 weeks).,

^{18}

liraglutide 3.0 mg daily ( 56 weeks),

^{19}

semaglutide 2.4 mg weekly ( 68 weeks),

^{20}

and tirzepatide 15 mg weekly ( 72 weeks).

^{21}

No long-term clinical trials are available for phentermine. No data were reported for

\geq 15 %

\geq 25 %

weight reduction for orlistat;

\geq 20 %

\geq 25 %

weight reduction for phentermine-topiramate, naltrexone-bupropion, and liraglutide; or

\geq 25 %

weight reduction for semaglutide.
32/360 毫克每日總劑量（56 週）。

^{18}

利拉魯肽 3.0 毫克每日（56 週），

^{19}

塞馬魯肽 2.4 毫克每週（68 週），

^{20}

以及替爾帕肽 15 毫克每週（72 週）。

^{21}

目前沒有關於芬特明的長期臨床試驗。對於

\geq 15 %

或

\geq 25 %

奧利司他減重的數據未報告；

\geq 20 %

或

\geq 25 %

芬特明-托吡酯、納曲酮-布普利昂和利拉魯肽的減重數據；或

\geq 25 %

塞馬魯肽的減重數據。
approximately

30 %

of dietary fat, leading to a caloric deficit.

^{12}

A separate treatment, cellulose-citric acid hydrogel, is administered like an oral medication and after ingestion, expands to occupy

25 %

of the stomach’s volume, promoting a sensation of fullness and increased satiety.

^{13}

This hydrogel was FDA-cleared as a device (manufacturers pursue clearance if the device is similar to other legally marketed devices, which differs from approval).

^{14}

大約

30 %

的膳食脂肪，導致熱量赤字。

^{12}

另一種治療，纖維素-檸檬酸水凝膠，像口服藥物一樣給予，並在攝入後膨脹以佔據

25 %

的胃部容量，促進飽腹感和增加飽足感。

^{13}

此水凝膠已獲得 FDA 批准作為一種設備（製造商如果設備與其他合法銷售的設備相似，則追求批准，這與認可不同）。

^{14}

Orlistat 奧利司他

Orlistat has been approved for adults since 1999 and for adolescents since 2003. Although most guidelines support its use in treating obesity in adults or adolescents,

^{6 - 8, 10}

the American Gastroenterological Association (AGA) guidelines recommended against orlistat due to its small effect on weight loss and adverse Gl effects.

^{9}

A meta-analysis of 52 RCTs that included 16964 participants reported that orlistat was associated with

3.1 %

greater weight reduction than placebo (

95 % Cl, 2.7 % - 3.5 %

) among adults with obesity.

^{15}

Nearly 70% of orlistat participants achieved 5% or greater weight loss (Figure 2),

^{16 - 21}

and adolescents had significant decreases in BMI (eTable 1 in the Supplement).

^{22}

奧利司他自 1999 年起獲准用於成人，自 2003 年起獲准用於青少年。儘管大多數指導方針支持其用於治療成人或青少年的肥胖，

^{6 - 8, 10}

美國腸胃病學會（AGA）指導方針卻建議不使用奧利司他，因為其對減重的效果微小且有不良的腸胃道副作用。

^{9}

一項包含 16964 名參與者的 52 項隨機對照試驗的綜合分析報告顯示，奧利司他與

3.1 %

安慰劑相比，在肥胖成人中與體重減輕有更大關聯（

95 % Cl, 2.7 % - 3.5 %

）。

^{15}

近 70%的奧利司他參與者達到了 5%或更高的體重減輕（圖 2），

^{16 - 21}

而青少年則在 BMI 上有顯著下降（補充資料中的 eTable 1）。

^{22}

Orlistat reduced waist circumference by approximately 10 cm , systolic blood pressure (SBP) by approximately 6 mm Hg , and lowdensity lipoprotein cholesterol (LDL-C) by approximately 9% among adults with obesity (Table 1).

^{16, 23 - 29}

Among patients with hypertension, a meta-analysis of 4 RCTs that included 2058 participants reported that orlistat was associated with 2.6 mm Hg greater decrease in SBP compared with placebo (

95 % Cl, 1.4 - 3.8

^{30}

In a 4 -year RCT, orlistat was associated with a

37.3 %

lower risk of incident type 2 diabetes compared with placebo (absolute 4 -year incidence of type 2 diabetes: orlistat,

6.2 %

; placebo,

9.0 %

^{23}

In a meta-analysis of 7 RCTs that included 1363 patients with type 2 diabetes, orlistat was associated with 2.0 kg greater weight loss (

95 %

Cl, 1.3 - 2.8

) and

0.5 %

greater hemoglobin

A_{1 c}

reduction (

95 % Cl

,
奧利司他在肥胖成人中使腰圍減少約 10 厘米，收縮壓（SBP）減少約 6 毫米汞柱，低密度脂蛋白膽固醇（LDL-C）減少約 9%（表 1）。在高血壓患者中，一項包含 2058 名參與者的 4 項隨機對照試驗（RCT）荟萃分析報告顯示，奧利司他與安慰劑相比，SBP 的減少量大約多了 2.6 毫米汞柱。在一項為期 4 年的隨機對照試驗中，奧利司他與安慰劑相比，發生 2 型糖尿病的風險降低（4 年內 2 型糖尿病的絕對發生率：奧利司他，

6.2 %

；安慰劑，

9.0 %

）。在一項包含 1363 名 2 型糖尿病患者的 7 項隨機對照試驗的荟萃分析中，奧利司他與安慰劑相比，體重減輕多了 2.0 公斤，並且血紅蛋白的減少量更大。

0.3 % - 0.6 %

) than placebo.

^{31} An RCT

to test the effects of orlistat on cardiovascular events has not been completed.

0.3 % - 0.6 %

) 比安慰劑更好。

^{31} An RCT

測試奧利司他對心血管事件的影響尚未完成。

Despite its modest effects on weight loss, orlistat typically has cardiometabolic benefits, including lowering SBP, hemoglobin

A_{1 c}

, and LDL-C. Orlistat is also associated with prevention of type 2 diabetes. Orlistat may be most appropriate for patients who would benefit from the cardiometabolic effects of orlistat but do not tolerate or have contraindications to other AOMs (Table 2).

^{12, 25 - 29, 32 - 38}

However, adherence to orlistat has been poor. In a large US health system, no patients prescribed orlistat continued to take the drug after 12 months.

^{39}

Reasons for orlistat discontinuation were not reported.

^{39}

儘管奧利司他對減重的效果有限，但通常具有心代謝益處，包括降低收縮壓、血紅蛋白

A_{1 c}

和低密度脂蛋白膽固醇。奧利司他還與預防 2 型糖尿病相關。奧利司他可能最適合那些能從奧利司他的心代謝效益中受益，但無法耐受或對其他抗肥胖藥物有禁忌的患者（表 2）。

^{12, 25 - 29, 32 - 38}

然而，對奧利司他的依從性一直很差。在美國一個大型健康系統中，沒有患者在 12 個月後繼續服用奧利司他。

^{39}

奧利司他停藥的原因未被報告。

^{39}

Gl adverse effects, including oily fecal spotting (27%), fecal urgency (

22 %

), and steatorrhea (

20 %

), are common in the first year of orlistat use, but typically resolve within 4 weeks

^{12}

and can be reduced by adhering to a low-calorie diet with less than

30 %

of calories from fat (Table 3).

^{12, 40}

Because of its mechanism of action, orlistat should be administered with meals containing some fat (10%

30 %

of calories) to be effective and limit adverse effects.
胃腸道不良反應，包括油性糞便斑點（27%）、糞便急迫感（

22 %

）和脂肪瀉（

20 %

），在使用奧利司他的一年內很常見，但通常在 4 週內會解決

^{12}

，並且可以通過遵循低熱量飲食來減少，該飲食中來自脂肪的熱量少於

30 %

（表 3）。

^{12, 40}

由於其作用機制，奧利司他應與含有一定脂肪的餐食一起服用（10%

30 %

的熱量），以便有效並限制不良反應。

Cellulose-Citric Acid Hydrogel
纖維素-檸檬酸水凝膠

Cellulose-citric acid hydrogel was FDA-cleared for adults in 2019.

^{13}

AGA guidelines stated that there was insufficient evidence to recommend its use.

^{9}

In a 24 -week RCT, compared with placebo, the hydrogel achieved

2.1 %

greater mean weight loss and GI adverse effects were common (43%).

^{41}

Product availability is unclear because the manufacturer filed for bankruptcy in October 2023.
纖維素-檸檬酸水凝膠於 2019 年獲得 FDA 批准用於成人。

^{13}

AGA 指導方針指出，沒有足夠的證據來推薦其使用。

^{9}

在一項為期 24 週的隨機對照試驗中，與安慰劑相比，該水凝膠實現了

2.1 %

更大的平均體重減輕，且腸胃不良反應很常見（43%）。

^{41}

產品的可用性不明，因為製造商於 2023 年 10 月申請破產。

Centrally Acting Medications
中樞作用藥物

FDA-approved AOMs that act on the central nervous system include phentermine, phentermine-topiramate, and naltrexonebupropion. These medications have various mechanisms of action in the brain. Combination regimens, such as phenterminetopiramate and naltrexone-bupropion, were developed to provide
FDA 批准的作用於中樞神經系統的 AOM 包括芬特明、芬特明-托吡酯和納曲酮-布普洛尼。這些藥物在大腦中具有不同的作用機制。組合療法，如芬特明-托吡酯和納曲酮-布普洛尼，旨在提供

Table 1. Weight and Cardiovascular Risk Factor Outcomes

^{a}

of Antiobesity Medications in Adults With Obesity and Without Diabetes by Mechanism of Action
表 1. 抗肥胖藥物在有肥胖且無糖尿病的成年人中按作用機制的體重和心血管風險因素結果

^{a}

complementary effects to enhance weight loss. Phentermine is a sympathomimetic amine that primarily increases norepinephrine in the hypothalamus with lesser effects on dopamine and serotonin.

^{42}

Although other sympathomimetic adrenergic agents are available
輔助效果以增強減重。苯丁胺是一種交感神經興奮劑胺，主要在下丘腦中增加去甲腎上腺素，對多巴胺和血清素的影響較小。

^{42}

雖然還有其他交感神經興奮劑可用
(eg, diethylpropion), this review focuses only on phentermine because it is the most commonly used AOM in this category of drugs.

^{43, 44}

Information about phentermine may not apply to other sympathomimetics, such as diethylpropion or benzphetamine.

^{45}

（例如，二乙基丙酮），本評論僅專注於芬特明，因為它是這類藥物中最常用的 AOM。

^{43, 44}

有關芬特明的信息可能不適用於其他交感神經興奮劑，例如二乙基丙酮或苯氟胺。

^{45}

Table 2. Individualizing Selection of Antiobesity Medications Among Specific Populations With Obesity Common in Primary Care Settings

^{a}

表 2. 在初級護理環境中針對特定肥胖人群個性化選擇抗肥胖藥物

Abbreviations: BP, blood pressure; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate; FDA, US Food and Drug Administration; HR, heart rate; HTN, hypertension.
縮寫：BP，血壓；CAD，冠狀動脈疾病；eGFR，估計腎小球過濾率；FDA，美國食品藥品監督管理局；HR，心率；HTN，高血壓。

^{a}

Guidelines from the American Association of Clinical Endocrinologists/ American College of Endocrinology and Obesity Canada suggest preferred antiobesity medications to use in certain patient populations,

^{7, 8}

which have been adapted for use in this table, along with information from package inserts and recent clinical trials. Specific medications are suggested for use in certain patient populations based on mechanisms of action, organ clearance, weight loss efficacy, adverse effects, warnings and contraindications, and available data for use of the medication within each population. Suggested use should not be interpreted to indicate FDA approval to treat the condition (eg, orlistat is not approved to treat HTN).

^{a}

美國內分泌學會/美國內分泌學與肥胖加拿大學院的指導方針建議在某些患者群體中使用首選的抗肥胖藥物，

^{7, 8}

這些建議已被調整以用於本表中，並附有來自包裝插頁和最近臨床試驗的信息。根據作用機制、器官清除、減重效果、不良反應、警告和禁忌症，以及在每個群體中使用該藥物的可用數據，建議在某些患者群體中使用特定藥物。建議的使用不應被解釋為 FDA 批准治療該病症（例如，奧利司他並未獲得批准用於治療高血壓）。

^{b}

Suggestions applicable to patients with moderate kidney impairment (eGFR

^{b}

適用於中度腎功能不全患者的建議 (eGFR

30 - 49 mL / \min

). For patients with severe kidney impairment (eGFR

< 30 mL / \min

), caution and close monitoring should occur if orlistat, liraglutide, semaglutide, or tirzepatide is used. Phentermine-topiramate and naltrexone-bupropion should be avoided in patients with severe kidney impairment.

^{7}

30 - 49 mL / \min

). 對於重度腎功能不全的患者（eGFR

< 30 mL / \min

），如果使用奧利司他、利拉魯肽、塞馬魯肽或提澤帕肽，應謹慎並密切監測。對於重度腎功能不全的患者，應避免使用芬特明-托吡酯和納曲酮-布普利昂。

^{7}

^{c S Suggestions applicable to patients with mild to moderate hepatic impairment}

(Child-Pugh score of 5-9). For patients with severe hepatic impairment (Child-Pugh score of >9), antiobesity medications should generally be avoided in the primary care setting.

^{7}

^{c S Suggestions applicable to patients with mild to moderate hepatic impairment}

（Child-Pugh 分數為 5-9）。對於重度肝功能不全的患者（Child-Pugh 分數 >9），在初級護理環境中通常應避免使用抗肥胖藥物。

^{7}

^{d}

Only a small percentage of participants in randomized controlled trials of listed medications were older adults and subgroup analyses with this population have not been published. Therefore, there are limited data within this population. Guidelines recommend that antiobesity medications be used with extra caution in older adults.

^{7}

^{d}

在列出藥物的隨機對照試驗中，只有一小部分參與者是老年人，且針對這一人群的亞組分析尚未發表。因此，該人群內的數據有限。指導方針建議在老年人中使用抗肥胖藥物時要格外謹慎。

^{7}

Phentermine has relatively low potential for abuse (Schedule IV), and signs of phentermine misuse or physical dependence have not been reported.

^{42}

Topiramate augments

γ

-aminobutyrate activity and inhibits a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/ kainite excitatory glutamate receptors

^{6}

; therefore, phenterminetopiramate works through several central mechanisms to reduce appetite and increase satiety. Naltrexone and bupropion reduce appetite and food cravings through different mechanisms that stimulate proopiomelanocortin neurons.

^{6}

苯特明的濫用潛力相對較低（第四類藥物），並且尚未報告苯特明濫用或身體依賴的跡象。

^{42}

托吡酯增強

γ

-氨基丁酸活性並抑制α-氨基-3-羥基-5-甲基-4-異噁唑丙酸/凱那酸興奮性谷氨酸受體

^{6}

；因此，苯特明-托吡酯通過幾種中樞機制來減少食慾並增加飽腹感。納曲酮和布普洛尼通過不同的機制刺激前腦啡肽神經元來減少食慾和食物渴望。

^{6}

Phentermine 芬特明

Phentermine was approved in the US for short-term use (3 months or fewer) in 1959, and therefore, its long-term use is considered off-label.

^{32, 33, 42}

The EndocrineSociety and AGA guidelines recommend long-term phentermine use to treat obesity in adults without cardiovascular disease.

^{6, 9}

Few RCTs have tested the efficacy and safety of phentermine for more than 3 months

^{45}

and long-term trials are needed for the FDA to consider extending the approved duration of use. One 6 -month RCT reported that phentermine 7.5 mg was associated with

5.5 %

weight loss and phentermine 15 mg was associated with

6.1 %

weight loss, which were significantly greater than

2.3 %

weight loss with placebo.

^{24}

More than

40 %

of participants achieved

5 %

or greater
苯丁胺於 1959 年在美國獲准短期使用（3 個月或更少），因此其長期使用被視為非標籤使用。內分泌學會和 AGA 指導方針建議在沒有心血管疾病的成年人中長期使用苯丁胺來治療肥胖。很少有隨機對照試驗測試苯丁胺超過 3 個月的療效和安全性，並且需要長期試驗以便 FDA 考慮延長批准的使用期限。一項為期 6 個月的隨機對照試驗報告指出，苯丁胺 7.5 毫克與體重減輕相關，苯丁胺 15 毫克與體重減輕相關，這些減輕的體重顯著大於安慰劑的體重減輕。超過參與者達到或超過。
weight loss with either dose of phentermine at 6 months.

^{24}

Another RCT reported that phentermine 15 mg reduced weight by

4.1 %

compared with

0.6 %

for placebo at 6-month follow-up.

^{46}

在 6 個月內，使用任一劑量的苯特明減重。

^{24}

另一項隨機對照試驗報告指出，15 毫克的苯特明在 6 個月的隨訪中相比於安慰劑減少了

4.1 %

的體重。

^{46}

There is little evidence regarding cardiometabolic outcomes with phentermine. A large observational study reported that phentermine use for more than 3 months was associated with greater weight reduction without increased risk of adverse cardiovascular events at 3 -year follow-up.

^{47}

No elevations in blood pressure were reported with phentermine use for 6 months and SBP decreased with its use (Table 1).

^{24, 46, 47}

關於苯丁胺的心臟代謝結果證據很少。一項大型觀察性研究報告指出，使用苯丁胺超過 3 個月與更大的體重減輕相關，且在 3 年隨訪中未增加不良心血管事件的風險。

^{47}

使用苯丁胺 6 個月未報告血壓升高，且使用後收縮壓下降（表 1）。

^{24, 46, 47}

Phentermine is the most inexpensive AOM for patients without insurance coverage for AOMs (Table 3). Clinicians should check that local regulations permit long-term prescribing of phentermine (eg, state medical and pharmacy boards) and should counsel patients about the off-label use, limited clinical trial data supporting long-term use, and unknown cardiovascular risks.
芬特明是對於沒有 AOM 保險覆蓋的患者來說最便宜的 AOM（表 3）。臨床醫生應檢查當地法規是否允許長期開處方芬特明（例如，州醫療和藥房委員會），並應向患者諮詢關於非標籤使用、支持長期使用的臨床試驗數據有限以及未知的心血管風險。

Few or no serious adverse events occurred in studies with a duration of 6 months or longer.

^{24, 46, 47}

Common adverse effects are xerostomia (

7 % - 12 %

), insomnia (

6 % - 11 %

), headache (

10 % - 12 %

), and constipation (4%-8%),

^{24, 32, 33, 46}

which may improve with dose reduction (Table 3). Phentermine may be unavailable in some countries outside the US where regulators have concerns about an
在持續 6 個月或更長時間的研究中，幾乎沒有或沒有嚴重的不良事件發生。

^{24, 46, 47}

常見的不良反應包括口乾（

7 % - 12 %

）、失眠（

6 % - 11 %

）、頭痛（

10 % - 12 %

）和便秘（4%-8%），

^{24, 32, 33, 46}

這些情況可能會隨著劑量減少而改善（表 3）。在一些對於藥物安全性有顧慮的美國以外的國家，芬特明可能無法獲得。

Medication, US approved population, and cost $^{a}$
藥物、美國批准的人口和成本 $^{a}$ Administration and titration
管理和滴定 Drug interactions 藥物相互作用 Patient populations with obesity
肥胖患者群體 Strategies to improve safety and tolerability related to common adverse effects
改善與常見不良反應相關的安全性和耐受性的策略

Consider use 考慮使用 Use with caution 小心使用 Avoid use $^{b}$ 避免使用 $^{b}$

Orlistat \({ }^{12}\) \(\geq 12\) y \$675/mo Discounts/coupons available online to reduce to approximately \$200/mo; generic formulations may be available in some countries

口服片劑與含脂肪的餐食一起服用，每天三次（120 毫克）製造商建議的劑量調整：無

Oral tablet taken with fat-containing meals 3 times a day ( 120 mg )

Manufacturerrecommended titration: none

Levothyroxine Warfarin Amiodarone Cyclosporine AEDs Antiretroviral drugs
左甲狀腺素華法林氨碘酮環孢素抗癲癇藥逆轉錄病毒藥物

成人：2 型糖尿病以降低 A

A_{c}

高血壓以降低血壓高脂血症以降低低密度脂蛋白 2 型糖尿病預防體重維持青少年

Adults with:

type 2 diabetes to lower A

A_{c}

HTN to lower BP

HLD to lower LDL

type 2 diabetes

prevention

Weight-loss

maintenance

Adolescents

歷史：頻繁腹瀉草酸鈣腎結石在高脂飲食（例如，低碳水化合物、酮飲食）後出現的腸胃道副作用增加

History of:

Frequent diarrhea

Oxalate nephrolithiasis

Following a high-fat diet (eg, low-CHO, ketogenic) as increased GI side effects

吸收不良膽汁淤積的歷史

History of:

Malabsorption

Cholestasis

建議：均衡、低熱量飲食，脂肪熱量佔比低於 30%，以減少腸胃不良反應。腸胃不良反應通常在 4 週內減輕。睡前服用含有多種維生素的脂溶性維生素（A、E、D、K、β-胡蘿蔔素），以避免缺乏

Counsel on:

Balanced, low-calorie diet with < 30% of calories from fat to reduce GI adverse effects

GI adverse effects typically subside within 4 weeks

Take MVI-containing fat-soluble vitamins (A, E, D, K, beta-carotene) at bedtime to avoid deficiencies

\begin{aligned} Phentermine^{32, 33} \\ \geq 16 y \\ $ 40 - $ 95 / mo \\ Discounts/coupons \\ available online to \\ reduce to approximately \\ $ 8 / m o; generic \\ formulations may be \\ available in some \\ countries \end{aligned}

每日早上服用口服片或膠囊（

15 mg, 30 mg

，或 37.5 毫克

)^{c}

口服片每日最多服用 3 次

(8 mg)^{c}

製造商建議的劑量調整：無

Oral tablet or capsule taken daily in the morning (

15 mg, 30 mg

JAMA | Review Medications for Obesity A Review JAMA | 評論 肥胖藥物的回顧